Accumulation of α-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy

Abstract

Recently, we have shown that the precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP), also known as alpha-synuclein, is a major component of Lewy bodies (LBs) as well as neuronal and glial cytoplasmic inclusions in multiple system atrophy (MSA). To elucidate whether the accumulation of NACP is specific to LB disease and MSA, we further studied 83 autopsied cases with various neurological disorders, using anti-NACP antibodies. In LB disease, NACP immunoreactivity was present in all of the LBs and Lewy neurites in both the central and peripheral nervous systems, the pale bodies in the substantia nigra, and dystrophic neurites in the hippocampal CA2/3 region. Immunoelectron microscopy revealed that the reaction product was localized within filamentous structures and associated granular structures. In MSA, NACP immunoreactivity was found in the intracytoplasmic inclusions of both neuronal and oligodendroglial cells, neuronal intranuclear inclusions, and swollen neuronal processes. No NACP immunoreactivity was found in a variety of other neuronal or glial inclusions in other disorders, including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, motor neuron disease and triplet-repeat diseases. These findings strongly suggest that the accumulation of NACP is a cytopathological feature common to LB disease and MSA.

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

“…The complete list of genes that were significantly changed by aging, including gene identifier numbers, can be found in the supporting information. immunoreactive with antibodies against Alpha synuclein (34,35). The heart has dual sympathetic and parasympathetic innervation, and recent findings have linked Alpha synuclein expression in the heart with sympathetic cardiac dysfunction in Parkinson's disease patients (36).…”

Direct Transfer of α-Synuclein from Neuron to Astroglia Causes Inflammatory Responses in Synucleinopathies

“…In PD and DLB, extensive ␣-synuclein-positive astroglial inclusion bodies have been documented in cortical and subcortical regions (4,6,7). In multiple system atrophy, another synucleinopathy, ␣-synuclein-positive inclusions, called glial cytoplasmic inclusions, are generated in oligodendrocytes (44). Astrocytes and oligodendrocytes appear to express ␣-synuclein protein, but the level of expression is much lower than in neurons (9,10).…”

Mutant and Wild Type Human α-Synucleins Assemble into Elongated Filaments with Distinct Morphologies in Vitro

“…First, anti-␣-synuclein antibodies stain LBs more intensely and consistently than any other antibodies, including anti-ubiquitin antibodies (12,(15)(16)(17)19). Second, anti-␣-synuclein immunoreactivity also is abundant in pale bodies (19,24), which are believed to be precursor lesions of LBs. Third, neurofilaments, another filamentous component of LBs (29 -31), are detected only in a small percentage of pale bodies (32), and most anti-neurofilament antibodies only label a subset of LBs (30).…”